Abstract
TDP-43 has recently been described as the major component of the inclusions found in the brain of patients with a variety of neurodegenerative diseases, such as frontotemporal lobar degeneration and amyotrophic lateral sclerosis. TDP-43 is a ubiquitous protein whose specific functions are probably crucial to establishing its pathogenic role. Apart from its involvement in transcription, splicing and mRNA stability, TDP-43 has also been described as a Drosha-associated protein. However, our knowledge of the role of TDP-43 in the microRNA (miRNA) synthesis pathway is limited to the association mentioned above. Here we report for the first time which changes occur in the total miRNA population following TDP-43 knockdown in culture cells. In particular, we have observed that let-7b and miR-663 expression levels are down- and upregulated, respectively. Interestingly, both miRNAs are capable of binding directly to TDP-43 in different positions: within the miRNA sequence itself (let-7b) or in the hairpin precursor (miR-663). Using microarray data and real-time PCR we have also identified several candidate transcripts whose expression levels are selectively affected by these TDP-43-miRNA interactions.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Base Sequence / genetics
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Cell Line, Tumor
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Down-Regulation / genetics
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Dyrk Kinases
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Epoxide Hydrolases / genetics
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Gene Expression / genetics
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Gene Expression Regulation / genetics*
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Genes, Reporter / genetics
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HeLa Cells
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Humans
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Laminin / genetics
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Luciferases / genetics
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Luciferases / metabolism
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Protein Binding / genetics
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Protein Serine-Threonine Kinases / genetics
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Protein-Tyrosine Kinases / genetics
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Qa-SNARE Proteins / genetics
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Small Interfering / genetics
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Ribonuclease III / metabolism
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Up-Regulation / genetics
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Vesicle-Associated Membrane Protein 3 / genetics
Substances
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DNA-Binding Proteins
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Laminin
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MicroRNAs
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Qa-SNARE Proteins
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RNA, Messenger
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RNA, Small Interfering
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Recombinant Proteins
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VAMP3 protein, human
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Vesicle-Associated Membrane Protein 3
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laminin gamma 1
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mirnlet7 microRNA, human
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Luciferases
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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DROSHA protein, human
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Ribonuclease III
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Epoxide Hydrolases
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EPHX1 protein, human